Role of epidermal growth factor receptor-tyrosine kinase inhibitors in the management of central nervous system metastases in epidermal growth factor receptor mutation-positive nonsmall cell lung cancer patients.

Abstract

Metastases to central nervous system (CNS) are very common in nonsmall cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-positive mutation. Brain is the most affected part of CNS where blood-brain barrier (BBB) presents a challenge to currently available chemotherapeutic agents as well as first- (erlotinib and gefitinib) and second (afatinib)-generation EGFR tyrosine kinase inhibitors (TKIs) due to their poor penetrability. A rapid development of EGFR T790M secondary mutation is another cause of treatment failure, and patients tend to progress despite initial response to first- and second-generation EGFR TKIs. Moreover, conventional treatments with heavy dose of radiation have a number of side effects compared to benefits attained. Recently, third-generation EGFR TKIs have been developed with proven efficacy in various clinical setups against EGFR mutation-positive cases of brain metastases in NSCLC. One such agent, osimertinib, is available in India. It has not only better penetration ability to BBB compared to other EGFR TKIs but also has significantly increased potency for most prevalent EGFR T790M mutations. Furthermore, it is active in patients who progress upon first- and second-generation EGFR TKIs. The purpose of this review article is to present an updated clinical preview of EGFR TKIs over conventional treatment, mainly radiation therapy to consider them as "use first" agents against EGFR T790M mutation in the treatment of patients with advanced NSCLC.